Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers.

Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments.

Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.

Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but the overall response rates are still limited. The combination of checkpoint blockade with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells has shown anti-tumor activity in human trials. However, the further clinical development of these antibodies has been hampered by significant off-tumor toxicities.

Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

Objectives: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children.

Methods: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection.

Effectiveness and Safety of Balloon Pulmonary Angioplasty for the Treatment of Patients with Persistent Pulmonary Hypertension after Pulmonary Endarterectomy.

(1) Background: Pulmonary endarterectomy (PEA) is the "gold standard" treatment for operable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Persistent pulmonary hypertension (PH) after PEA confers a worse prognosis. Balloon pulmonary angioplasty (BPA) could represent a useful therapy in this setting, but evidence about its effectiveness and safety in patients with previous PEA is limited.

Tumor targeted 4-1BB agonist antibody-albumin fusions with high affinity to FcRn induce anti-tumor immunity without toxicity.

Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies (mAbs) has shown anti-tumor activity in human trials, but can be associated with significant off-tumor toxicities involving FcγR interactions. Here, we introduce albumin-fused mouse and human bispecific antibodies with clinically favorable pharmacokinetics designed to confine 4-1BB costimulation to the tumor microenvironment. These Fc-free 4-1BB agonists consist of an EGFR-specific V antibody, a 4-1BB-specific scFv, and a human albumin sequence engineered for high FcRn binding connected in tandem (LiTCo-Albu).

Applications of trimerbodies in cancer immunotherapy.

Trimerbodies, with their unique structural and functional properties, are the basis of a new generation of therapeutic antibodies, which due to their small size and plasticity are ideal for the generation of novel biological protein drugs with multiple competitive advantages over conventional full-length monoclonal antibodies. Since their emergence, trimerbodies have been used in preclinical cancer diagnosis and therapy. Trimerbodies are highly adaptable molecules, as they allow target-specific modulation of T cell-mediated anti-tumor immunity to enhance preexisting responses or to generate de novo immune responses.

Engineered mRNA and the Rise of Next-Generation Antibodies.

Monoclonal antibodies are widely used as therapeutic agents in medicine. However, clinical-grade proteins require sophisticated technologies and are extremely expensive to produce, resulting in long lead times and high costs. The use of gene transfer methods for in vivo secretion of therapeutic antibodies could circumvent problems related to large-scale production and purification and offer additional benefits by achieving sustained concentrations of therapeutic antibodies, which is particularly relevant to short-lived antibody fragments and next-generation, Fc-free, multispecific antibodies.

Characterization of New Proteomic Biomarker Candidates in Mucopolysaccharidosis Type IVA.

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the -acetylgalactosamine-6-sulfatase () gene. Skeletal dysplasia and the related clinical features of MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance. Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests.

GMP-Compliant Manufacturing of NKG2D CAR Memory T Cells Using CliniMACS Prodigy.

Natural killer group 2D (NKG2D) is a natural killer (NK) cell-activating receptor that recognizes different stress-induced ligands that are overexpressed in a variety of childhood and adult tumors. NKG2D chimeric antigen receptor (CAR) T cells have shown potent anticancer effects against different cancer types. A second-generation NKG2D CAR was generated by fusing full-length human NKG2D to 4-1BB costimulatory molecule and CD3ζ signaling domain.

Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer's Disease Patients. Relevant Role of Neutrophils in Oxidative Stress.

Since aging is considered the most risk factor for sporadic Alzheimer's Disease (AD), the age-related impairment of the immune system (immunosenescence), based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD) and severe AD, and of age-matched controls (elderly healthy subjects) as well as of adult controls.

2013 ACR/EULAR systemic sclerosis classification criteria in patients with associated pulmonary arterial hypertension.

Objective: To analyze the performance of the 1980 ACR and new 2013 ACR/EULAR criteria for systemic sclerosis (SSc) in cutaneous SSc (lcSSc) patients, especially those affected by lcSSc and pulmonary arterial hypertension (PAH).

Methods: All patients with a clinical lcSSc diagnosis from a prospective observational SSc cohort were included. Sociodemographic and disease-related variables were collected, and PAH confirmed by right heart catheterization (RHC).

Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis.

Objectives: To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Doppler-echocardiography (TTE) in patients with early systemic sclerosis (SSc).

Methods: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with <3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected.

Validation of the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis in patients from a capillaroscopy clinic.

Objective: To validate the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in patients from a capillaroscopy clinic.

Methods: All patients attended in a capillaroscopy clinic were included. Sociodemographic and SSc-related variables were collected.

Quality of life of institutionalized older adults by dementia severity.

Background: The goal of the study was to analyze the factors associated with quality of life (QoL) in institutionalized older adults with dementia, based on self and proxy ratings, and if these characteristics differ by dementia severity.

Methods: Cross-sectional study of 525 people with dementia (PwD) and their caregivers (professional or family caregivers). Two different QoL questionnaires, leading to three measures, were used: QoL in Alzheimer's disease scale (QOL-AD), self and proxy-rated, and QoL in late-stage dementia scale (QUALID), proxy-rated.

Staphylococcus aureus abscesses: methicillin-resistance or Panton-Valentine leukocidin presence?

Introduction: Panton-Valentine leukocidin (PVL) is a toxin associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) worldwide and also occurs in community-associated methicillin-susceptible S aureus (CA-MSSA) strains. The aims of the study were to determine the prevalence of PVL in community-onset S aureus skin and soft-tissue infections (SSTIs) and to analyse the influence of methicillin resistance and PVL presence on the clinical characteristics of these infections.

Patients And Methods: We prospectively enrolled all children with S aureus community-onset SSTIs attending the emergency department of a tertiary hospital between 2007 and 2009.

Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles.

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.

WT 1 expression in nevi and melanomas: a marker of melanocytic invasion into the dermis.

Background: WT1, first recognized as a tumor suppressor gene involved in the development of Wilms' tumor, may have apparently contradictory findings and functions. As WT1 has been identified as a molecular target for cancer immunotherapy, immunodetection of WT1 in tumor cells has become an essential step in cancer studies.

Methods: We compare the expression of this protein among different types of melanocytic nevi and among stages in primary melanoma progression.

Subcutaneous atypical fibrous histiocytoma.

Benign fibrous histiocytoma is one of the most frequent benign neoplasms mainly composed of a mixture of fibroblastic and histiocytic cells, especially found in the skin (dermatofibroma), particularly in the limbs. The diagnosis of cutaneous benign fibrous histiocytoma is generally easy; however, rare variants may be difficult to identify, and the diagnosis only confirmed after exhaustive histopathological examination. Thus, deep subcutaneous dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans and dermatofibroma with monster giant cells from malignant fibrous histiocytoma and atypical fibroxanthoma.

Antidepressant combinations: epidemiological considerations.

Objective: To evaluate the treatment options in patients who do not respond appropriately to a single antidepressant alone.

Method: The medical literature was reviewed.

Results: A number of strategies are available if a patient fails to respond adequately to initial antidepressant treatment, including the combination with another psychoactive drug.

Lhermitte-Duclos disease and Cowden disease: clinical and genetic study in five patients with Lhermitte-Duclos disease and literature review.

Background: Lhermitte-Duclos Disease (LDD) is an infrequent cerebellar disorder characterized by focal or diffuse enlargement of cerebellar folia presenting as a slowly growing mass in the posterior fossa. Over the past decade its association with Cowden disease (CD) has been recognized with increasing frequency. This latter disease is a genetic condition leading to the presence of multiple hamartomas and neoplasias which affect mainly the skin, thyroid, breast and genito-urinary and gastro-intestinal tracts.